JAK1
JAK1 is an essential Janus kinase that mediates biologic responses downstream of class II cytokine receptors, γc-containing receptors, and gp130-dependent receptors[1]. Mechanistically, the JAK/STAT pathway provides a rapid membrane-to-nucleus signaling module that drives transcriptional programs linked to inflammation, immunity, cancer, and autoimmune disease[2]. In inflammatory contexts, JAK1 transduces signals from γc cytokines, IL-6, interferons, and IL-10, connecting cytokine receptor activation to immune-cell regulation and synovial inflammation[3]. Disease models and human genetics support this role, because JAK1 gain-of-function variants drive immune dysregulation with atopic dermatitis, allergy, eosinophilia, and gastrointestinal inflammation[4][5]. Compared with related isoforms, JAK1 shows nonredundant signaling, and Jak1 has a dominant role over Jak3 in γc receptor signaling[1][6]. JAK2 more directly supports hematopoietic growth-factor pathways, whereas JAK3 is mainly linked to common γc receptor biology[3][6]. For experimental applications, selective JAK1 inhibitors help separate cytokine-driven inflammatory signaling from broader JAK blockade[7]. Chemical proteomics identified an allosteric cysteine in JAK1 C817, absent from JAK2 and JAK3, enabling inhibitors that block JAK1-dependent trans-phosphorylation and cytokine signaling[8].
References:
- [1]. Rodig SJ, et al. Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses. Cell. 1998 May 1;93(3):373-83. [Content Brief]
- [2]. Hu X, et al. The JAK/STAT signaling pathway: from bench to clinic. Signal Transduct Target Ther. 2021 Nov 26;6(1):402. [Content Brief]
- [3]. Spinelli FR, et al. JAK1: Number one in the family; number one in inflammation? Rheumatology (Oxford). 2021 May 5;60(Suppl 2):ii3-ii10. [Content Brief]
- [4]. Del Bel KL, et al. JAK1 gain-of-function causes an autosomal dominant immune dysregulatory and hypereosinophilic syndrome. J Allergy Clin Immunol. 2017 Jun;139(6):2016-2020.e5. [Content Brief]
- [5]. Fayand A, et al. Successful treatment of JAK1-associated inflammatory disease. J Allergy Clin Immunol. 2023 Oct;152(4):972-983. [Content Brief]
- [6]. Haan C, et al. Jak1 has a dominant role over Jak3 in signal transduction through γc-containing cytokine receptors. Chem Biol. 2011 Mar 25;18(3):314-23. [Content Brief]
- [7]. Schwartz DM, et al. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017 Dec;16(12):843-862. [Content Brief]
- [8]. Kavanagh ME, et al. Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine. Nat Chem Biol. 2022 Dec;18(12):1388-1398. [Content Brief]
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JAK1 Related Products (149)
Related Products (149)
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Recombinant Proteins (4)
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Antibodies (2)
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Fezakinumab
0 ImagesSynonyms: ILV 094Fezakinumab (ILV 094) is an anti-IL-22 monoclonal antibody. Fezakinumab inhibits IL-22 signal transduction, and regulates the JAK1/STAT3 pathway as well as apoptotic proteins. Fezakinumab alleviates airway remodeling, alveolar enlargement and inflammatory cell infiltration in lung tissues. Fezakinumab reduces the levels of neutrophils, lymphocytes, eosinophils and macrophages in lung tissues. Fezakinumab can be used in the research of chronic obstructive pulmonary disease and skin diseases.
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Oclacitinib
0 ImagesSynonyms: PF-03394197
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Oclacitinib monomaleate
0 ImagesSynonyms: PF-03394197 monomaleate
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Atinvicitinib
0 ImagesAtinvicitinib is an orally active and selective JAK1 inhibitor. Atinvicitinib blocks signaling of JAK1-dependent pruritogenic and pro-inflammatory cytokines, including those in the IL-31, IL-4, and IL-13 pathways. Atinvicitinib can be used for the researches of pruritus associated with allergic dermatitis and canine atopic dermatitis.
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VVD-118313
0 ImagesVVD-118313 (compound 5a) is a potent, selective JAK1 inhibitor. VVD-118313 targets an isoform-restricted allosteric cysteine to block JAK1-dependent trans-phosphorylation and cytokine signaling. VVD-118313 can be used for research of cancer. VVD-118313 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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Ivarmacitinib
0 ImagesSynonyms: SHR0302Ivarmacitinib (SHR0302) is a potent and orally active all members of the JAK family inhibitor, particularly JAK1. The selectivity of Ivarmacitinib for JAK1 is >10-fold for JAK2, 77-fold for JAK3, 420-fold for Tyk2. Ivarmacitinib inhibits JAK1-STAT3 phosphorylation and induces the apoptosis of hepatic stellate cells. Ivarmacitinib has anti-proliferative and anti-inflammatory effects.
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PROTAC JAK1 degrader 1
0 ImagesPROTAC JAK1 degrader 1 is a JAK1 PROTAC degrader with a DC50 of 214 nM and an IC50 of 5.2 nM. PROTAC JAK1 degrader 1 inhibits the downstream JAK-STAT signaling pathway by degrading JAK1. PROTAC JAK1 degrader 1 exhibits antiproliferative activity in cells. PROTAC JAK1 degrader 1 can be used for research on leukemia.
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Cadefrecitinib
0 ImagesSynonyms: GLPG3667Cadefrecitinib (GLPG3667) is a reversible, ATP-competitive and orally active TYK2 inhibitor with an IC50 of 2.3 nM. Cadefrecitinib inhibits IFNα/pSTAT1, and the IC50 values in human peripheral blood mononuclear cell (PBMC) and whole blood assays are 70 nM and 623 nM, respectively. Cadefrecitinib has the potential for the study of inflammatory and autoimmune diseases.
